The past year was one of tremendous challenges and changes, and it served as a resounding reminder that our health cannot be taken for granted. For our team at Orchard, this year also brought reflections on our past as well as new possibilities for our future.

In 2015, I, together with close colleagues, co-founded Orchard Therapeutics with a vision of bringing hematopoietic stem cell (HSC) gene therapy to patients with devastating genetic diseases. Over the course of my 25+ year journey in gene therapy, I’ve witnessed firsthand the tremendous, potentially transformative impact of our HSC approach on severe immunological and neurometabolic conditions. And today, five years into our growth as a company, Orchard is strategically approaching a new horizon, which will bring us even closer to realizing the full potential of our ex vivo HSC gene therapy approach.

This month, after years of partnership with San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), Orchard received European Commission (EC) approval for our first therapy for the treatment of eligible patients with metachromatic leukodystrophy (MLD). This is an extraordinary achievement given the transformative potential of HSC gene therapy and severity of many rare inherited diseases.

Looking ahead, we’ve already begun charting a path from clinical validation in ultra-rare diseases like MLD toward less rare neurodegenerative, neurometabolic and immunological genetic diseases such as a genetic subset of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and a genetic subset of Crohn’s disease. With our deep understanding of HSC gene therapy and its ability to deliver therapeutic genes to multiple different tissues and organs, together with regulatory and commercial validation from our recent EC approval, we are well positioned to expand our HSC gene therapy approach to these larger indications.

Orchard’s gene therapy pipeline, as well as the nearly 400 other gene therapies in clinical development, offer potentially transformative therapies for life-threatening conditions with high unmet need, if approved. However, these investigational treatments will have little value if they never reach patients that need them. Health care systems around the world must prepare for the flood of new, potentially curative treatments by improving newborn screening (NBS) and other diagnostic initiatives and supporting access. At the same time, companies in the field, such as Orchard, must continue to evaluate and implement innovative processes and technologies to increase manufacturing capacity and enable commercial scalability so that we’re ready to bring these gene therapies to a larger number of patients in the future.

Advancing NBS so that it that keeps pace with innovation will help ensure infants with rare, genetic diseases can benefit from one-time, potentially curative gene therapies. Orchard, along with EveryLife Foundation for Rare Diseases and several industry partners, recently announced a joint effort to assess the capacity of NBS in the United States. The evaluation, due to be released in April 2021, will recommend a policy roadmap to strengthen the NBS system for all infants across the country – with the goal of early and definitive diagnosis of all infants suffering from the kinds of devastating genetic diseases we are working to treat. Additionally, we are actively supporting researchers in Europe and the US to pilot the use of a NBS assay for MLD to help build a key evidence base required by governments to consider adding MLD to their NBS panel at the national or local level.

To increase our manufacturing efficiency and scalability, we have made exciting investments in stable cell lines for viral vector production as well as in improving the way HSCs are transduced. We have the opportunity now, while our patient populations remain small, to make our manufacturing as efficient as possible while ensuring adherence to manufacturing standards, so that we are ready for the growth in production needed to bring approved gene therapies to a larger number of patients in the future.

A great deal of work is also underway to explore and test new ideas that may help evolve health systems to support patient access to potentially transformative therapies. We are collaborating with multi-stakeholder forums on both sides of the Atlantic – including MIT’s New Drug Development Paradigms (NEWDIGS) Financing and Reimbursement of Cures in the US (FoCUS) Project, the EURODIS’ Rare Impact Project as well as gene and cell therapy initiatives organized by the Alliance for Regenerative Medicine (ARM) and the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE) – to help advance these critical efforts.

Looking ahead to 2021 and beyond, the future is bright. While we have much work to do to realize the full potential of our HSC gene therapy platform approach, tremendous progress has been made in expanding our pipeline to less rare diseases with high unmet need, and we have continued our work in newborn screening, our investments in manufacturing, and our collaboration in access and reimbursement. No matter the challenges that the new year may bring, we remain committed to advancing HSC gene therapies to make them available for all patients who could benefit, and we are well positioned to do just that.